ABSTRACT There is a great need for quick tests that identify treatment response in Alzheimer's disease (AD) to determine who benefits from the treatment. In this study, A Quick Test of cognitive speed (AQT) was compared with the mini-mental state examination (MMSE) in the evaluation of treatment outcome in AD.
75 patients with mild to moderate AD at a memory clinic were assessed with AQT and the MMSE at a pretreatment visit, at baseline and after 8 weeks of treatment with cholinesterase inhibitors (ChEI) initiated at baseline. Changes in the mean test scores before and after treatment were compared, as well as the number of treatment responders detected by each test, according to a reliable change index (RCI).
After 8 weeks of treatment, the AQT improvement, expressed as a percentage, was significantly greater than that of the MMSE (P = 0.026). According to the RCI, the cut-offs to define a responder were ≥16 seconds improvement on AQT and ≥3 points on the MMSE after 8 weeks. With these cut-offs, both tests falsely classified ≤5% as responders during the pretreatment period. After 8 weeks of treatment, AQT detected significantly more responders than the MMSE (34% compared with 17%; P = 0.024). After 6 months of treatment, the 8-week AQT responders still showed a significantly better treatment response than the AQT nonresponders (22.3 seconds in mean difference; P < 0.001).
AQT detects twice as many treatment responders as the MMSE. It seems that AQT can, already after 8 weeks, identify the AD patients who will continue to benefit from ChEI treatment.

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Knowledge of longitudinal progression in mild Alzheimer's disease (AD) is required for the evaluation of disease-modifying therapies. Our aim was to observe the effects of long-term cholinesterase inhibitor (ChEI) therapy in mild AD patients in a routine clinical setting.
This was a prospective, open-label, non-randomized, multicenter study of ChEI treatment (donepezil, rivastigmine or galantamine) conducted during clinical practice. The 734 mild AD patients (Mini-Mental State Examination (MMSE) score 20 to 26) were assessed at baseline and then semi-annually over three years. Outcome measures included the MMSE, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinician's Interview-Based Impression of Change (CIBIC) and Instrumental Activities of Daily Living (IADL) scale.
After three years of ChEI therapy, 31% (MMSE) and 33% (ADAS-cog) of the patients showed improved/unchanged cognitive ability, 33% showed improved/unchanged global performance and 14% showed improved/unchanged IADL capacity. Higher mean dose of ChEI and lower educational level were both predictors of more positive longitudinal cognitive and functional outcomes. Older participants and those with a better IADL score at baseline exhibited a slower rate of cognitive decline, whereas younger participants and those with higher cognitive status showed more preserved IADL ability over time. Gender and apolipoprotein E (APOE) genotype showed inconsistent results. Prediction models using the abovementioned scales are presented.
In naturalistic mild AD patients, a marked deterioration in IADL compared with cognitive and global long-term outcomes was observed, indicating the importance of functional assessments during the early stages of the disease. The participants' time on ChEI treatment before inclusion in studies of new therapies might affect their rate of decline and thus the comparisons of changes in scores between various studies. An increased understanding of expected disease progression in different domains and potential predictors of disease progression is essential for assessment of future therapies in AD.

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ABSTRACT Background: A Quick Test of Cognitive Speed (AQT) is a brief test that can identify cognitive impairment. AQT has been validated in Arabic, English, Greek, Japanese, Norwegian, Spanish, and Swedish. The aim of this study was to develop Italian criterion-referenced norms for AQT. Methods: AQT consists of three test plates where the patient shall rapidly name (1) the color of 40 blue, red, yellow, or black squares (AQT color), (2) the form of 40 black figures (circles, squares, triangles, or rectangles; AQT form), (3) the color and form of 40 figures (consisting of previous colors and forms; AQT color-form). The AQT test was administered to 121 Italian cognitively healthy primary care patients (age range: 45-90 years). Their mean Mini-Mental State Examination (MMSE) score was 28.8 ± 0.9 points (range 26-30 points). AQT naming times in seconds were used for developing preliminary criterion cut-off times for different age groups. Results: Age was found to have a significant moderate positive correlation with AQT naming times color (r = 0.65, p < 0.001), form (r = 0.53, p < 0.001), color-form (r = 0.63, p < 0.001) and a moderate negative correlation with MMSE score (r = -0.44, p < 0.001) and AQT naming times differed significantly between younger (45-55 years old), older (56-70 years old), and the oldest (71-90 years old) participants. Years of education correlated positively but weakly with MMSE score (r = 0.27, p = 0.003) and negatively but weakly with AQT color (r = -0.16, p = ns), form (r = -0.24, p = 0.007), and color-form (r = -0.19, p = 0.005). We established preliminary cut-off times for the AQT test based on +1 and +2 standard deviations according to the approach in other languages and settings. Conclusions: This is the first Italian normative AQT study. Future studies of AQT - a test useful for dementia screening in primary care - will eventually refine cut-off times for normality balancing sensitivity and specificity in cognitive diagnostics.

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State Examination (MMSE) [15]. It is also the recom-mended cognitive test for the evaluation of treatmentwith ChEI, according to the National Institute for Healthand Clinical Excellence (NICE) [5]. This makes MMSE asuitable reference test to compare with the AQT.An optimal cognitive evaluation test of treatmentresponse will, at a given cut-off, classify very few patientsas treatment responders when no treatment is given andas many as possible when treatment is given. To definethe cut-off for treatment response, one must considerfactors such as cognitive fluctuation of the patients, lowtest reliability, training effect, and so on. These factorscause changes in test score that are not caused by thetreatment and therefore must be accounted for. Themost common way of doing that is by establishing a reli-able change index (RCI) [16]. RCI is a statistical analysisfor detecting individually significant change, and it hasbeen used in more than 500 medical studies.The aim of this study was to1. Compare the changes of AQT and the MMSEbefore and after ChEI treatment in AD patients.2. Compare the ability of AQT and the MMSE todetect treatment responders according to cut-offs calcu-lated by RCI analyzes.Materials and methodsPatientsThe AD patients were enrolled from a part of the Swed-ish Alzheimer’s Treatment Study (SATS) located in thetown of Malmö, Sweden [17]. SATS is a prospective,open-label study in routine clinical settings, which havecollected patients who have been referred to the MemoryClinic at Malmö University Hospital and have met thecriteria for AD according to NINCDS-ADRDA [18]. Inaddition to a clinical examination by physicians specializ-ing in dementia disorders, the patients were examinedwith brain computed tomography, routine blood samples,and cerebrospinal fluid analysis. After the baseline visit,treatment with rivastigmine, donepezil, or galantaminewas initiated. The patients were followed up in a struc-tured program with assessments at baseline, 8 weeks,6 months, and semiannually thereafter. For patients to beenrolled from SATS to this study, they had to haveMMSE and AQT color-form (AQT-CF) scores from avisit at a predefined time period of 1 to 6 months beforebaseline, the baseline visit, and the visit at 8 weeks afterbaseline. The MMSE and AQT scores had to be from thesame occasions. Only patients with an MMSE score of13 points or more and an AQT-CF score of 190 secondsor less at baseline were included because test changes aredifficult to assess in patients with very poor test perfor-mance, because of low reliability [19]. The cut-offs werepredefined and not based on the current study popula-tion, which otherwise could introduce selection bias. Theinclusion criteria generated a study population of 75 ADpatients. They had been followed at the clinic over amean ± standard deviation (SD) period of 32 ± 19months and had been reviewed by the study doctors S.P.and O.H. from a longitudinal perspective in regard todiagnosis accuracy. All patients lived at home and had amean age of 77 ± 6.7 years. Seventy-one percent werewomen. Sixty-five percent were treated with galantamine,18% with rivastigmine, and 17% with donepezil. Themean doses of the drugs during the 8 weeks of treatmentwere 9.9 mg, 3.7 mg, and 5.4 mg, respectively.A written informed consent was obtained from allpatients and proxies. The study was approved by theethics committee of Lund University, Sweden, and wascarried out in accordance with the Helsinki Declaration.MMSE and AQTSpecialized dementia nurses administered both testsaccording to standardized guidelines to maximizeinterrater reliability. The attention part of the MMSEFigure 1 A sample of AQT. Each original test plate contains 40 figures. The patient is instructed to quickly name the color of each figure on thefirst test plate (AQT-C), the form on the second plate (AQT-F), and the color and form on the third plate (AQT-CF) [8]. Only AQT-CF results wereanalyzed in this study.Palmqvist et al. Alzheimer’s Research & Therapy 2010, 2:29http://alzres.com/content/2/5/29Page 2 of 8

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was scored by the serial subtraction of 7 from 100 [20].The backward spelling was used if the patient couldnot perform simple arithmetic exercises [21].AQT measures attention and cognitive speed, hasshown high test-retest reliability (r = 0.91 to 0.95), andexhibits no habituation or learning in repeated trialsover 10 minutes [22]. AQT-CF has been validatedagainst WAIS-III P IQ (r = -0.61; P < 0.01), MMSE (r =-0.72; P < 0.01) and ADAS-cog (r = 0.63; P < 0.01; cor-relation made after 6 months of ChEI treatment in AD)[12,23]. It has shown no significant correlation with theTrail Making Test (TMT), verbal association fluency(FAS), or Rey Complex Figure Test (RCFT) [12]. Thetest scores constitute the number of seconds it takes fora patient to complete each test plate (Figure 1). The testwas performed in Swedish, which has produced thesame results as a test performed in English [10]. OnlyAQT-CF was analyzed in this study because it is themost validated and sensitive part of AQT and containsthe cognitive measures that are mostly associated withAD [22].Assessing test changes: Reliable Change IndexRCI provides a confidence interval (CI), which repre-sents the predicted changes that would occur if apatient’s test score does not change significantly fromone assessment to another. The most commonly usedCI is 90% [24-27], which was also used in this study.With this CI, about 5% in a stable control group willshow a test improvement (according to a cut-off valuebased on the RCI), even when no intervention or realchange has occurred. The RCI is calculated from a con-trol group by considering the test-retest reliability, SD,and a systematic bias of the score change between thefirst and second test occasion (for example, trainingeffect or disease progression) [24]. The formulae thatdescribe this can be found in Additional file 1. Insteadof calculating the RCI based on changes in a healthycontrol group, the RCI was calculated from the changesof the AD patients during the untreated period. TheMMSE and AQT changes from before baseline to base-line were thus used to calculate an interval of “normal”test changes when no treatment was given (that is, theRCI). Test changes during the treatment period greaterthan the RCI were considered to be due to treatmenteffect. By using the same population as controls (theperiod from before baseline to baseline) and as cases(the period from baseline to postbaseline), one elimi-nates many confounding factors such as test-score varia-bility (which is more pronounced in AD than in healthycontrols), age, disease progression, gender, and so on.Because of the clinical nature of this study, the testinterval before treatment varied from 1 to 6 months,with a mean ± SD interval of 3.7 ± 1.2 months. Becauseof the progressive nature of AD, a longer prebaselinetest interval would likely show a greater deterioration.Therefore, an approximated score at 8 weeks beforebaseline was calculated for each patient. The 8 weeksprebaseline score was calculated in the following way:8 × (baseline score - prebaseline score)/Number ofweeks between the prebaseline and baseline visit. Theseapproximated scores were then used to calculate thetest changes during 8 weeks before treatment (baselinescore - 8 weeks prebaseline score), which provided asingle test-retest interval to be compared with thechanges after 8 weeks of treatment.For patients with a test interval of 1 to 3 monthsbefore baseline, the mean 8 weeks prebaseline MMSEscore was 22.7 ± 3.3 points, and the mean 8 weeks pre-baseline AQT-CF score was 97.3 ± 22.8 seconds. Thosewith an interval of 4 to 6 months before baseline had amean 8 weeks prebaseline MMSE score of 23.1 ± 3.1points and a mean prebaseline AQT-CF score of 99.4 ±21.4 seconds. No significant differences were foundbetween the groups regarding the calculated 8 weeksprebaseline MMSE and AQT scores (P > 0.50). Conse-quently, the fact that AQT and the MMSE were admi-nistered at different intervals before treatment did notseem to have any impact on the calculated 8 weeks pre-baseline scores. Previous RCI studies have also used avaried interval between test occasions, but without cor-recting for this (calculating a single test-retest interval)or testing the homogeneity of the group [24,26,27]. Webelieve our method provides a more valid RCI resultbecause the calculations are based on the same interval(8 weeks without treatment) to which it is going to beapplied (8 weeks with treatment).Statistical analysisThe RCI was calculated as described in previous studies(see Additional file 1) [27]. Variables that followed anormal distribution were analyzed with parametricstatistics, and significantly skewed variables, with non-parametric statistics. The MMSE and AQT changeswere assessed with the Wilcoxon matched-pairs signedranks test. The test changes expressed as percentageswere analyzed with the paired t test. The McNemar testwas used when comparing the number of MMSE andAQT responders. Linear relations were examined byusing Pearson correlation. The statistical analyses wereperformed by using Statistical Package for SocialSciences (SPSS) software (version 17.0; SPSS Inc.,Chicago, IL).ResultsChanges in test scoresThe MMSE and AQT scores are shown in Table 1. It isimportant to note that a negative AQT change and aPalmqvist et al. Alzheimer’s Research & Therapy 2010, 2:29http://alzres.com/content/2/5/29Page 3 of 8

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positive MMSE change stand for improvement. Duringthe 8-week pre-baseline period when the patients hadnot yet received any treatment, mean AQT deterioratedsignificantly by 2.6 seconds (P < 0.05), whereas themean MMSE deteriorated nonsignificantly by -0.29points (P = 0.09). After 8 weeks of treatment, the meanAQT score improved by -9.7 seconds compared withbaseline (P < 0.0001), and the mean MMSE scoreimproved 0.6 points (P < 0.05; Table 1).To compare the test changes of MMSE and AQT in astatistical manner, the score changes of each patientmust be expressed as a percentage of the previous scorebecause the tests consist of different scales (Figure 2).When just comparing the AQT and MMSE changes aftertreatment, AQT indicated a somewhat more pronouncedimprovement than did the MMSE (P = 0.06). However, itis important to account for the individual disease-pro-gression rate (score change before treatment) becausethis affects the degree of change in test scores after treat-ment. The individual test changes of AQT and MMSEduring the 8 weeks before treatment were thus sub-tracted from the changes after 8 weeks of treatment. Thismeant that if a patient deteriorated 5% in a test scorebefore treatment and improved 10% after treatment, thetotal treatment effect was an improvement of 15%(assuming that the patient would continue to deteriorate5% during the 8 weeks after baseline if no treatment hadbeen given). After correcting for individual disease pro-gression, AQT improved by 10.8%, and the MMSEimproved by 3.7% (Figure 2) When analyzing thesevalues, the improvement of AQT was significantly greaterthan that of the MMSE (95% CI of the difference: 0.9% to13.3%; P = 0.026).Treatment responders according to the Reliable ChangeIndexThe Reliable Change Index (RCI) results are summarizedin Figure 3. The test-retest reliability (Pearson correla-tion) used in the RCI formula was based on the baselineand 8-week pre-baseline occasions. The correlation coef-ficient of AQT was 0.87 (P < 0.001), and for the MMSE,0.86 (P < 0.001). The 90% CI to state if a significantchange had occurred on an individual basis (the RCI) was-15.5 to +20.5 seconds for AQT. That is, if a patientimproved more than -15.5 seconds, a significantimprovement had occurred (clinically this meant thateveryone with a -16-second improvement, because onlywhole seconds were measured). Patients who improvedTable 1 Mean MMSE and AQT values ± standard deviationVariable8 weeks before baselineen = 75Baselinen = 7522.7 ± 3.0a101.5 ± 24.9c*8 weeks after baselinen = 7523.3 ± 3.5b*91.8 ± 28.4d*The MMSE, pointsAQT Color-Form, seconds23.0 ± 3.198.8 ± 21.6aP = 0.088 compared with 8 weeks before baseline.bP = 0.047 compared with baseline.cP = 0.045 compared with 8 weeks before baseline.dP < 0.0001compared with baseline.eCalculated value for all 75 patients according the description in Materials and methods. *Significant change.Calculated with the Wilcoxon test. MMSE, the Mini-Mental State Examination (0 to 30 points); a higher score indicates better cognition. AQT, A Quick Test ofcognitive speed (measured in seconds); less time indicates better cognition.Figure 2 Mean values of the score changes expressed as percentages. The lines show the changes from 8 weeks before baseline tobaseline and from baseline to 8 weeks after baseline. Dashed lines represent assumed deterioration without treatment. Error bars representstandard error of the mean.1Comparison of the AQT and MMSE improvements after treatment when accounting for disease progression(calculated with paired samples t test).Palmqvist et al. Alzheimer’s Research & Therapy 2010, 2:29http://alzres.com/content/2/5/29Page 4 of 8

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significantly were denoted “responders”. For the MMSE,the RCI was -2.99 to +2.41 points (that is, those with atleast a +3-point improvement were responders). After8 weeks of treatment, AQT detected 26 treatmentresponders (34%), whereas the MMSE detected 13 (17%)treatment responders (Figure 3). As expected accordingto the RCI, both test cut-offs falsely classified ≤5%responders during the pretreatment period (Figure 3). A“false responder” in this case is a patient who improvedmore than the RCI during the period when no treatmentwas given. After treatment, ≤5% of all the patients dete-riorated more than the RCI of AQT and the MMSE,which also is just as expected.Unsurprisingly, the AQT-treatment respondersshowed greater improvement after 8 weeks of treatmentcompared with the nonresponders in mean AQT score(P < 0.0001). However, a major significant difference inmean AQT change between the groups was still foundFigure 3 Responders. Percentage responders after 8 weeks without treatment and after 8 weeks with treatment according to cut-offs derivedfrom RCI. Details on the RCI analysis can be found in Additional file 1. Calculated with the McNemar test.Palmqvist et al. Alzheimer’s Research & Therapy 2010, 2:29http://alzres.com/content/2/5/29Page 5 of 8

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after 6 months of treatment. The AD patients who wereclassified as treatment responders by AQT after 8 weeksof treatment showed a mean improvement of -19.3 ±22.3 seconds on AQT after 6 months of treatment. Thenonresponders, conversely, deteriorated 3.3 ± 13.5 sec-onds over the 6-month treatment period. Thus, theAQT responders at the 8-week visit continued clearly toshow a better treatment response at the 6-month visitcompared with the nonresponders (P < 0.0001).DiscussionIn this study, we evaluated AQT as a test for detectingearly ChEI treatment response in AD and compared itwith the MMSE. After 8 weeks of treatment, AQT hadimproved significantly more than the MMSE whenaccounting for disease progression (Figure 2). Further,AQT identified twice as many treatment responders as didthe MMSE (34% compared with 17%; p = 0.02; Figure 3).The increased number of responders cannot be explainedby low reliability or random changes of AQT scores,because AQT classified only 5% (false) responders duringthe 8-week period before treatment (Figure 3). Finally,when comparing the AQT responders and nonrespondersfrom the 8-week visit, the responders still showed a signifi-cantly better treatment response after 6 months of treat-ment. This indicates that AQT detects early treatmentresponders who seem to continue to benefit from ChEItreatment.Evaluation of treatmentGood clinical practice and cost-benefit considerationsrequire that all AD patients be evaluated before and afterthe initiation of treatment to determine whether thetreatment shall continue [5]. The most common test forthis evaluation in clinical practice is the MMSE, and thisis also the recommended test according to the NICEguidelines [5]. In clinical trials, the ADAS-cog is the mostcommonly used cognitive test [28,29]. It measures abroader span of cognitive functions, but has the disad-vantage of taking 45 minutes to administer comparedwith 3 to 5 minutes for AQT and 10 to 15 minutes forthe MMSE. Because of the length of the ADAS-cog, itcannot really be regarded as a brief cognitive test suitablefor clinical practice. ADAS-cog and the MMSE are wellstudied for ChEI evaluation of AD, but no previousstudies of AQT were performed in this context. However,in a recent randomized, placebo-controlled, multinationalstudy, AQT was used to evaluate the treatment effect ofmemantine on dementia with Lewy bodies and Parkinsondisease dementia [30]. In that study, both AQT and theglobal cognitive measure CGIC improved significantlyafter 24 weeks of treatment, compared with placebo,whereas the MMSE failed to improve significantly.Future evaluation issuesIn the future, it is likely that more patients with mildcognitive impairment (MCI) will be included in thera-peutic trials and treated in clinical practice. It is thenessential to have a sensitive test with no ceiling effect.The MMSE and the ADAS-cog have detected in MCIstudies significant cognitive changes [31,32], but theyhave also been criticized for their ceiling effects andinability to detect small cognitive changes [28]. In theonly study in which AQT has been used to evaluateMCI treatment, AQT improved significantly, whereasthe other cognitive tests failed to do so (WAIS III DigitSpan, WAIS-R NI Spatial Span, Digit Symbol Modalities,and Rey’s Complex Figure Test) [33]. Further, AQT hasno ceiling effect and, in this study, was able to signifi-cantly detect the subtle disease progress of AD duringthe nontreatment period of 8 weeks (Table 1). Althoughthe results are promising, more studies are needed towarrant the sensitivity of AQT to cognitive change andto systematically compare it with the MMSE and theADAS-cog.Another important future issue is that by 2040, it ispredicted that 71% of all dementia patients will be indeveloping countries [34]. Therefore, the InternationalPsychogeriatric Association (IPA) and the Alzheimer’sAssociation have pointed out the need for a culturallyindependent test [7,28]. AQT has so far been validatedin Western, Arabic, and African countries and does notexhibit any culturally dependent questions or exercises[8,9,35], whereas the MMSE is affected by ethnicity[36,37].Detecting treatment respondersIn the present study, we evaluated the treatment responseafter 8 weeks. Previously, it was shown that 4 to 8 weeksof AD treatment results in a significant treatment effectcompared with placebo [38-41]. This supports our evalua-tion of treatment effects already after 8 weeks. It is also isin agreement with the guidelines by NICE and the Ameri-can College of Physicians (ACP) [5,7]. When evaluatingthe treatment response, the ACP has suggested that a 3-point change in the MMSE indicates a clinically significantchange [7]. This is also the same result as the presentstudy found to indicate a significant change (Figure 3).Unfortunately, no comparable studies are available regard-ing individual change on AQT.This study used a statistical method (RCI) to deter-mine treatment responders according to the MMSE andAQT. The clinical relevance of an MMSE improvementof at least 3 points or an AQT improvement of at least16 seconds is uncertain. In the entire population, theclinical relevance of a mean AQT improvement of10.8% and a mean MMSE improvement of 3.7% is alsoPalmqvist et al. Alzheimer’s Research & Therapy 2010, 2:29http://alzres.com/content/2/5/29Page 6 of 8

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uncertain. It is important to note that these values wereonly used to compare the MMSE and AQT as evalua-tion instruments. To determine a clinically meaningfulAQT or MMSE change, a minimal clinically importantdifference (MCID) must be defined. One approach todetermine the MCID for AD could be to measure thenatural history of decline over 12 months or longer in alarge group of patients by using AQT, the MMSE, and aglobal rating of the cognitive performance. A definitionof MCID could then be the percentage of change on theMMSE or AQT that is anchored against the natural his-tory of global change in AD.According to the cut-off values, AQT detected signifi-cantly more responders after 8 weeks of treatment thandid the MMSE (34% compared with 17%; P = 0.026),while falsely detecting 5% responders when no treat-ment was given (Figure 3). This indicates that AQT is amore-sensitive evaluation tool, which is further empha-sized by the changes on a group level. AQT improvedsignificantly more after treatment than did the MMSEwhen accounting for disease progression (Figure 2). Themore-pronounced sensitivity of AQT compared with theMMSE might be explained by their different scales andthe different cognitive functions that are measured. Stu-dies have shown that ChEI mostly improves attention[13,14], which is one of the main cognitive domainsmeasured by AQT. It is possible that the treatmentresponse in our study could have been higher if all ChEIdoses had been increased after 4 weeks of treatment(the dose was often increased after 8 weeks). Thisshould, however, not affect the comparison betweenAQT and the MMSE.Intuitively, it seems that patients who exhibit the rightcharacteristics initially to have a positive treatmentresponse would continue to benefit from the medica-tion. This assumption has been debated, and to deter-mine whether it is true, the reliability and validity of theevaluation instrument must be high. In our study, wefound that the AD patients who were classified as treat-ment responders by AQT after 8 weeks of treatmentstill performed significantly better on AQT after 6months, compared with the patients classified as nonre-sponders after 8 weeks (22.6 seconds in mean difference;P < 0.0001). This indicates that AQT might be usedafter 8 weeks of ChEI treatment to identify those whowill continue to benefit from the treatment.Two advantages of this study are that the treatmentwas evaluated prospectively and that the same populationwas used both as controls and as cases. The latter is themost important factor for reliable RCI results, as mostconfounding factors are eliminated. A shortcoming wasthat this was not a randomized study with a placebogroup, but instead a study with a control group. Thetreatment effect can therefore not with certainty be sepa-rated from the placebo effect. However, placebo treat-ment in clinical trials of AD patients has not resulted insignificant improvements of any cognitive tests [38-41].Furthermore, the lack of a placebo group should notaffect the comparison of the MMSE and AQT.ConclusionsIn conclusion, AQT, a quick test of cognitive speed andattention, seems to be twice as sensitive as the MMSEin detecting early treatment response to ChEI in ADpatients. The early responders detected by AQT contin-ued to benefit from ChEI after 6 months of treatment.This indicates the potential usefulness of AQT whenevaluating treatment effects in clinical routine, especiallyin primary care units. Moreover AQT may be importantwhen evaluating new treatments in the early stages ofAD, because of its sensitivity and lack of ceiling effect.Further studies are needed to compare the treatmentresponse detected by AQT and brief cognitive testsother than the MMSE.Additional materialAdditional file 1: Reliable Change Index (RCI). Statistical informationon how the RCI was calculated.AbbreviationsACP: American College of Physicians; AD: Alzheimer’s disease; AQT: A QuickTest of cognitive speed; AQT-C: A Quick Test of cognitive speed-Color(subtest 1); AQT-CF: A Quick Test of cognitive speed-Color Form (subtest 3);AQT-F: A Quick Test of cognitive speed-Form (subtest 2); ChEI: cholinesteraseinhibitors; CI: confidence interval; MMSE: the Mini-Mental State Examination;NICE: National Institute for Health and Clinical Excellence; NINCD-ADRDA:National Institute of Neurological and Communicative Disorders and Strokeand the Alzheimer’s Disease and Related Disorders Association; r: correlationcoefficient; RCI: Reliable Change Index; SD: standard deviation.AcknowledgementsFunding was obtained from Skåne University Hospital, Malmö, Sweden.Author details1Clinical Memory Research Unit, Department of Clinical Sciences Malmö,Lund University, S-205 02 Malmö, Sweden.2Neuropsychiatric Clinic, SkåneUniversity Hospital Malmö, 205 02 Malmö, Sweden.Authors’ contributionsSP participated in the design of the study, performed the statistical analysis,and drafted the manuscript. LM and EL participated in the design andcoordination of the study and revised the manuscript. CW revised thestatistical analysis and the manuscript. OH participated in the design of thestudy, helped out in the statistical analysis, and revised the manuscript. Allauthors read and approved the final manuscript.Competing interestsThe authors declare that they have no competing interests.Received: 18 February 2010 Accepted: 15 October 2010Published: 15 October 2010Palmqvist et al. Alzheimer’s Research & Therapy 2010, 2:29http://alzres.com/content/2/5/29Page 7 of 8